Category: 3. Business

Findings from a retrospective, real-world analysis conducted through the Polish Adult Leukemia Group showed that first-line treatment with the combination of venetoclax (Venclexta) and obinutuzumab (Gazyva) was efficacious and generally well tolerated in patients with chronic lymphocytic leukemia (CLL) who had significant preexisting comorbidities.¹

Data showed that response-evaluable patients (n = 199) achieved an overall response rate (ORR) of 97.4%, including a complete remission (CR) rate of 32.7%. Three patients experienced stable disease as best response. In 2 patients who had progressive disease, 1 had Richter transformation to diffuse large B-cell lymphoma.

At a median follow-up of 25.9 months (95% CI, 24.5-27.9), the median progression-free survival (PFS) and overall survival (OS) were both not reached. The estimated 1- and 2-year PFS rates were 93.9% (95% CI, 90.7%-97.2%) and 88.4% (95% CI, 83.9%-93.2%), respectively. The respective 1- and 2-year OS rates were 94.3% (95% CI, 91.3%-97.5%) at and 92.7% (95% CI, 89.2%-96.4%).

Regarding safety (n = 220), 99.5% of patients had completed therapy, including 78.1% who received the full 12 cycles of protocol treatment. Grade 3 or 4 adverse effects (AEs) occurred in 68.6% of patients. Additionally, 82.7% of patients received a final dose of venetoclax at 400 mg and did not require any dose reductions. In 15.9% of patients who had venetoclax dose reductions, the primary reasons comprised hematologic toxicity (74.3%), infections (5.7%), liver toxicity (5.7%), patient decision (5.7%), diarrhea (2.9%), and fatigue (2.9%). Notably, venetoclax was not given to 2 patients due to infection or immune thrombocytopenia after receiving obinutuzumab.

“The combination of venetoclax [and] obinutuzumab in de novo CLL is an effective and generally well-tolerated first-line therapy in…patients with significant comorbidities under real-world conditions,” lead study author Klaudia Zielonka, MD, of the Department of Hematology, Transplantation and Internal Medicine, at the Medical University of Warsaw in Poland, and colleagues wrote in a publication of the data. “TP53 aberrations did not affect early treatment outcomes; however, longer follow-up is mandatory.”

Real-World Study Background and Breakdown

The combination of venetoclax (Venclyxto) and obinutuzumab is currently approved in the European Union for the treatment of patients with previously untreated CLL, based on data from the phase 3 CLL14 study (NCT02242942).² In the United States, the combination was approved by the FDA for patients with CLL or small lymphocytic lymphoma in May 2019.³

However, study authors noted that prospective clinical trial inclusion and exclusion criteria could create patient selection bias, and they explained that real-world data could help confirm the efficacy and safety of the combination in an older patient population often burdened by comorbidities.¹

The retrospective study included adult patients with previously untreated CLL who started treatment with venetoclax plus obinutuzumab in Poland between November 2021 and August 2024. Patients needed to have an ECOG performance status of 2 or less, along with comorbidities, defined as a CIRS total score of more than 6 and/or a creatinine clearance of more than 30 mL/min and less than 70 mL/min.

Patients received obinutuzumab at 100 mg on cycle 1, day 1, and 900 mg on cycle 1, day 2, followed by a 1000-mg dose on days 8 and 15 of cycle 1, then day 1 of cycles 2 to 6. Venetoclax was ramped up at daily doses of 20 mg daily during the first week and gradually increased to 400 mg after 5 weeks, starting at day 22 of cycle 1. Patients received venetoclax for up to 12 cycles or until disease progression and/or unacceptable toxicity.

ORR, CR rate, PFS, OS, and safety were the primary objectives of the study.

In the safety population, patients had a median age of 70 years (range, 45-86), and 25.5% were at least 75 years of age. Most patients were male (60.9%), had an ECOG performance status of 1 (56.0%), had Binet stage C disease (50%), had Rai high stage disease (51.4%), and were at intermediate risk for tumor lysis syndrome (51.6%).

Notably, 10% of evaluable patients (n = 190) harbored 17p deletions and/or TP53 mutations. IGHV mutational status was evaluated in 51 patients, and 72.5% of this group harbored IGHV mutations. The median time from CLL diagnosis to treatment was 1.6 years (range, 0-19).

Efficacy Outcomes After Early Discontinuation

In patients who discontinued therapy early (n = 36) for reasons other than disease progression or death, 63.9% had decreased renal function, and 83.3% had a CIRS index higher than 6.

The ORR in this subgroup was 85.7%; however, the estimated 24-month PFS rate was 49.4% (95% CI, 34.5%-70.6%) in this population (HR vs patients who completed protocol therapy, 12.024; 95% CI, 5.498-26.297; P < .001). The 24-month OS rate was 66.5% (95% CI, 52.8%-83.7% [HR: 12.502; 95% CI, 4.720-33.116; P < .001]).

Additional Safety Data

The most common any-grade AEs included neutropenia (83.2%), thrombocytopenia (57.3%), anemia (54.5%), febrile neutropenia (10%), upper respiratory tract infections (7.7%), pneumonia other than COVID-19 (8.6%), COVID-19 hospitalization (11.8%), COVID-19 pneumonia (6.4%), autoimmune hemolytic anemia (4.1%), immune thrombocytopenia (2.7%), diarrhea (6.8%), liver toxicity (1.8%), increased alanine aminotransferase levels (6.4%), increased aspartate aminotransferase levels (7.3%), increased alkaline phosphatase levels (4.1%), increased gamma-glutamyl transferase (2.3%), atrial fibrillation (1.4%), acute coronary syndrome (0.5%), increased bilirubin concentration (2.3%), cutaneous toxicity (2.7%), obinutuzumab infusion-related reactions (9.5%), secondary malignancies (2.3%), fever (2.3%), peripheral edema (1.4%), and central nervous system disorders (0.9%).

Any-grade biochemical TLS occurred at a rate of 19.5%, and the rate of clinical TLS was 3.6%.

References

1. Zielonka K, Izdebski B, Drozd-Sokołowska J, et al. Venetoclax and obinutuzumab in first-line treatment of unfit patients with CLL – real-life data analysis of the Polish Adult leukemia group. Leuk Lymphoma. Published online August 1, 2025. doi:10.1080/10428194.2025.2535693
2. Venclyxto. European Medicines Agency. Accessed August 21, 2025. https://www.ema.europa.eu/en/documents/product-information/venclyxto-epar-product-information_en.pdf
3. FDA approves venetoclax for CLL and SLL. FDA. May 15, 2019. Accessed August 21, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-venetoclax-cll-and-sll

The U.S. government can work to prevent Chinese telecommunications equipment manufacturers from dominating the global market by promoting Open Radio Access Networking (Open RAN) standards worldwide. Radio access networks are a component of mobile infrastructure that connects user devices to the broader network. Open RAN is a technological standard for building that infrastructure using open, compatible interfaces, allowing hardware and software from different vendors to work together. While China’s mercantilist policies boost its manufacturers, such as Huawei and ZTE, enabling them to take ever-greater global market share, a wider adoption of Open RAN standards would level the playing field and allow the United States to restore its telecommunications equipment industry as a global competitor.

Open RAN standards represent a set of open, non-proprietary technological specifications for the hardware and software used in radio access networks. The standards are set by the O-RAN Alliance, an international group of mobile network operators, vendors, and research institutions.

As a concept, Open RAN allows wireless networks to function as “Lego blocks,” with separate but interoperable components. This feature enables network operators to buy equipment from any vendor and integrate with the rest of an Internet Service Provider’s (ISP’s) existing network’s hardware and software. Thus, it comprises a system that allows competition at all levels of components, enabling innovation among companies. This architecture differs from the status quo, which does not permit third-party vendors to participate in the network buildout. In contrast, China’s strategy of promoting Huawei and ZTE leverages the current RAN equipment market to lock in ISPs to cheap but vulnerable systems.

Open RAN concepts have been around for almost a decade, but adoption has been slow and skewed toward the U.S. market. Open RAN made up 7 to 10 percent of global revenues in 2024, and is expected to reach 20–30 percent by 2028. Several factors are impeding the global adoption of Open RAN systems.

First, for countries that have already deployed wireless infrastructure, converting their networks to Open RAN equipment is costly and does not offer an immediate source of new revenue. However, promoting the use of Open RAN standards in greenfield wireless markets, such as developing countries, presents a profit opportunity for Open RAN hardware and software companies as well as a more economically viable and secure competitor to Chinese offerings.

Second, some critics have voiced concerns that a network comprised of multiple vendors’ components will be less secure, as bad actors would have a wider attack surface. However, this view misjudges the tradeoff. Open RAN allows companies to pick and choose trusted vendors if certain ones are unreliable, unlike the status quo, in which developing countries often incur the full security threats posed by companies such as Huawei and ZTE.

The primary benefit of wider adoption of Open RAN networks for the United States can be to help restore the position of U.S. equipment and software companies, which has been lost to China-backed competitors. But Open RAN also provides technological advantages in and of itself. Despite concerns about a wider threat landscape, competition from a marketplace with more vendors and adequate standards will compel vendors to make their products more secure and reduce costs. Open RAN can also deliver a better quality of service and experience, enable greater automation of network functions, and facilitate faster innovation through the disaggregated network architecture.

Broader adoption of Open RAN systems worldwide is strategically important for the United States, both in terms of “defense” and “offense” perspectives in the techno-economic competition with China. On the “defense” side, Open RAN is crucial for countering China’s highly subsidized and predatory approach in telecommunication networks. While Chinese companies such as Huawei and ZTE promote full-stack RAN equipment, especially in greenfield markets in the Global South, they do so at the expense of U.S. national security (since Chinese Intelligence Law requires all companies to share information with the Chinese government) and harm Western competitors. Even U.S. allies such as Germany and Spain maintain Huawei within their telecommunication networks, although they have shown signs of phasing out the presence of Chinese equipment.

The U.S. government can take the “offensive” by helping boost America’s technological leadership and increase U.S. companies’ global market share through the adoption of Open RAN standards as part of trade negotiations. U.S. companies are equipped to play a greater role in the global RAN market by driving innovation in the use of virtualized networking components. However, this requires the U.S. government to lead a collective, public-private effort to promote Open RAN standards since adoption from market forces alone has been slow and ineffective.

To create a coherent foreign and trade policy approach that reinforces the already existing efforts to promote Open RAN worldwide, the U.S. government should do the following:

The U.S. Trade Representative’s Office (USTR) should initiate a Section 301 investigation into unfair foreign policies that distort competition or impede the adoption of Open RAN standards. This investigation could include assessing countries that are phasing out Huawei or ZTE, such as Germany, Spain, and other countries that heavily rely on these companies, such as Brazil, Indonesia, Malaysia, or Serbia.

The U.S. government should fulfill its commitments under the Information Technology Agreement (ITA) by recommitting to a zero-for-zero tariff regime on telecommunication equipment and other goods listed in the ITA. The United States is an exporter of goods relevant to the global adoption of Open RAN, including processors and controllers (over $24 billion of exports in 2023) and power and distribution panels (over $7 billion). Maintaining a zero-for-zero regime for ITA goods means maintaining competitiveness. Fulfilling ITA commitments would enable U.S. manufacturers of telecommunication equipment to access components and intermediate goods at competitive prices and avoid potential retaliation.

The U.S. government should provide more “muscle” to the International Development Finance Corporation (DFC) so it can issue loans, equity, and other foreign direct investment (FDI) to ease the adoption of Open RAN-compatible equipment and standards.

The U.S. Department of State should reinforce its “tech-diplomacy” efforts at the multilateral level, such as at the OECD, ITU, and APEC, and at the bilateral level, particularly in Global South countries with low Internet connectivity rates, such as India. While the U.S. government has taken some steps to promote Open RAN, this doesn’t seem to be a priority. The State Department’s Bureau of Cyberspace and Digital Policy (CDP), intended to centralize America’s cyber diplomacy, was downsized and pulled apart into multiple offices. The Technology Gateway Program (TECHGATE) seems to be a continuation of USAID’s “Digital Connectivity and Cybersecurity Partnership,” a program to build cybersecurity capacity in the Global South. TECHGATE’s funding opportunity does not include explicit metrics to include Open RAN technologies’ adoption as an outcome.

Open RAN standards can be an effective tool for countering Chinese tech dominance, and the United States should leverage that tool to protect its economic and national security.

Royal Mail missed its targets by delivering nearly a quarter of first class mail late in the first update since its parent company was bought by a Czech billionaire, figures show.

The company said on Friday it had delivered 75.9% of first class mail within one working day of collection in the three months to 29 June, up from 74.2% the previous quarter but well behind the 93% target set by the regulator, Ofcom.

Its performance on second class was “broadly stable”, with 89.3% of mail delivered within three working days, lagging Ofcom’s target of 98.5%.

EP, the group controlled by Daniel Křetínský, completed a drawn-out £3.6bn takeover of International Distribution Services (IDS) in April after a UK government review under national security laws. Křetínský, known as the Czech Sphinx, owns a collection of businesses including energy assets, and stakes in Sainsbury’s and West Ham United.

In its quarterly update, Royal Mail also said it had managed to deliver 97% of first class mail within three days.

The company has long struggled to deliver mail on time. It has been fined more than £16m over the past two years for failing to meet targets, and Ofcom began an investigation this year after it missed annual targets.

Jamie Stephenson, interim chief operating officer at Royal Mail, said: “Timely letter deliveries really matter to our customers, and they matter to us too.

“We are taking targeted steps to improve reliability, and we remain focused on delivering a better service for all our customers, every day.”

Last month, Royal Mail was given the green light by Ofcom to drop Saturday deliveries of second-class letters, and to provide services on alternate weekdays from Monday to Friday rather than every day as it attempts to cut costs and make the service more reliable.

Ofcom also lowered targets for first class post to be delivered the next day from 93% to 90%, and for second class within three days from 98.5% to 95%. The changes take effect from next April.

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Tom MacInnes, director of policy at Citizens Advice, said: “It’s no surprise that paying consumers are still being let down by our country’s postal service. For more than half a decade, late deliveries have disrupted lives – causing people to miss medical appointments and benefit decisions – while stamp prices soared.

“Yet, Ofcom has responded by lowering Royal Mail’s delivery targets and slashing its second class delivery requirements in half. These changes don’t guarantee a more reliable or affordable service, but risk making things worse for consumers.”

He added: “Ofcom must ensure reduced deliveries are balanced with targets Royal Mail genuinely has to hit so people finally get the service they deserve.”

Emma Gilthorpe suddenly left after just over a year as Royal Mail’s chief executive in June, weeks after EP completed its IDS takeover.